Chapter 23:
Metabolism of Mycobacterium tuberculosis

Affiliations: 1: Department of Clinical Sciences, London School of Hygiene and Tropical Medicine, Keppel Street, London WC1E 7HT, United Kingdom;
2: Department of Applied Biology, University of Hull, Hull HU6 7RX, United Kingdom

Researchers in mycobacterial biochemistry have almost exclusively concentrated their efforts on those aspects of metabolism that appear to be unique to members of the genus Mycobacterium and have, in the absence of information to the contrary, assumed that other aspects of metabolism will be more or less the same as those of other, more amenable bacteria. In this chapter, the authors have chosen to follow the same elective pathway, concentrating on those aspects of metabolism that appear to be at least in some way unique to the mycobacteria and are, moreover, of relevance to the growth of Mycobacterium tuberculosis as a pathogen within the tissues and fluids of its host. The peptidoglycan in mycobacteria is of a type common in many bacteria but with two slight differences. First, there are interpeptide linkages between two diaminopimelate residues as well as the usual D-alanyl-diaminopimelate linkages. Second, the usual N-acetylmuramic acid is replaced with N-glycolyl-muramic acid in M. bovis and in other mycobacteria. An approach that might be appropriate would be to make probes for M. tuberculosis DNA based on appropriate genes identified in muramic acid metabolism from other microbes, as these genes would be expected to have some sequence similarity in all bacteria. There are many interesting and important implications for the new field of mycobacterial genetics: the complex organization of these microbes demands multiple genes for fatty acid biosynthesis and seemingly innumerable glycosyltransferase genes.

Metabolism of host carbon sources by intracellular mycobacteria (adapted from Barclay and Wheeler [1989]). In addition, mycobacteria may also assimilate purines and pyrimidines and use these for nucleic acid biosynthesis. TCA, tricarboxylic acid.

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Figure 1

Metabolism of host carbon sources by intracellular mycobacteria (adapted from Barclay and Wheeler [1989]). In addition, mycobacteria may also assimilate purines and pyrimidines and use these for nucleic acid biosynthesis. TCA, tricarboxylic acid.

Structure of mycobactin, the intracellular siderophore of mycobacteria. For structures of other mycobactins, see Snow (1970) and Barclay et al. (1985). Substituents: R1, alkyl chain up to C19, often with double bond at cis &Delta;2 position, though occasionally, as with M. marinum, this can be CH3; R2, &mdash;H or &mdash;CH3; R3 &mdash;H or &mdash;CH3; R4, usually &mdash;CH3 or &mdash;C2H5, though occasionally, as with M. marinum, a long alkyl chain up to C17; R5, &mdash;H or &mdash;CH3. For M. tuberculosis, R1 is&mdash;C19H37, R2 = R3 = R5 = &mdash;H, and R4 is &mdash;CH3.

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Figure 3

Structure of mycobactin, the intracellular siderophore of mycobacteria. For structures of other mycobactins, see Snow (1970) and Barclay et al. (1985). Substituents: R1, alkyl chain up to C19, often with double bond at cis &Delta;2 position, though occasionally, as with M. marinum, this can be CH3; R2, &mdash;H or &mdash;CH3; R3 &mdash;H or &mdash;CH3; R4, usually &mdash;CH3 or &mdash;C2H5, though occasionally, as with M. marinum, a long alkyl chain up to C17; R5, &mdash;H or &mdash;CH3. For M. tuberculosis, R1 is&mdash;C19H37, R2 = R3 = R5 = &mdash;H, and R4 is &mdash;CH3.

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